There have been improvements in the management of acute transplant rejection over the last thirty years as seen in the increased survival of transplants during the first year following the procedure. However, the half-life for long term organ survival has not improved and only about 50% of the transplants are functional at ten years. Chronic transplant rejection, as opposed to acute transplant rejection, is the cause for the majority of transplant failures.
Acute transplant rejection occurs as a result of the immune system of the transplant recipient attacking the transplanted tissue. Acute rejection is rapid, generally occurs within hours to weeks after transplant of the tissue and can typically be suppressed with the use of immunosuppressive drugs such as cyclosporin A. Whereas acute rejection is suppressed with immunosuppressive protocols, treatment for chronic rejection is less well defined. Acute rejection and chronic rejection have significantly different characteristics as immune responses. For example, chronic rejection occurs over time, typically several months to years after engraftment, even in the presence of successful immunosuppression. It involves multiple factors and processes of the host and is usually the result of a prolonged process of wound healing the host undergoes post-transplant. Therefore, chronic rejection is not totally immunological in origin and additional causes(s) are not fully understood. They may include ischemic insult, denervation of the transplanted tissue, hyperlipidemia and hypertension associated with immunosuppressive drugs.
For most organs, the most definitive way of showing that rejection is occurring is by biopsy of that organ. For practical reasons, however, biopsies are not always done and are particularly less practical when chronic rejection is suspected. Chronic rejection of a transplant organ is generally characterized as failure of the organ after it has begun to perform its function in the recipient or host. Thus, chronic rejection is commonly monitored by a decrease in organ function which, if unarrested, results in failure of the organ, infection, and necrosis of organ tissue. Chronic rejection is identified, commonly too late for treatment that can save the transplant, by pathogenic fibrosis, which is characterized by extensive deposition of the extracellular matrix proteins: collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. Fibrosis becomes a telltale characteristic of chronic rejection where fibrogenesis is observed to damage organ microstructures or to block passages that need to remain open for organ function.
The chronic rejection process is not inhibited by any known therapeutic regimen at this time. Moreover, as noted above, it is sometimes difficult to detect and treat in a time frame that will save the transplant. Thus, additional improvements in the long-term survival of organ transplant patients are dependent on the development of new techniques for managing chronic transplant rejection.